反应详情

1,1,1-Trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-[({6-methyl-1-[3-(methyloxy)phenyl]-1H-indazol-4-yl}amino)methyl]-2-pentanol (Example 22, 46 mg, 0.085 mmol) was dissolved in anhydrous dichloromethane (4 ml) and cooled to −70° C. (cardice/acetone bath). Boron tribromide (1.0M in dichloromethane, 0.15 ml, 0.15 mmol) was added and the mixture allowed to warm to room temperature over 2 hours and then stirred for a further 20 hours. The mixture was cooled to −70° C. and more boron tribromide (1.0M in dichloromethane, 0.1 ml, 0.1 mmol) was added and the mixture was allowed to warm to room temperature and stirred for a further 20 hours. The mixture was cooled again to −70° C. and more boron tribromide (1.0M in dichloromethane, 0.1 ml, 0.1 mmol) was added and the mixture was allowed to warm to room temperature and stirred for a further 32 hours. The mixture was then diluted with dichloromethane (15 mL), cooled in ice and quenched with methanol (3 mL). After a further 15 min the mixture was partitioned between dichloromethane (35 mL) and aqueous sodium bicarbonate (35 mL). The organic phase was washed again with aqueous sodium bicarbonate (35 mL), passed through a hydrophobic frit and evaporated under reduced pressure to yield crude material. This crude product was purified by mass-directed autopreparation to give the title compound (9 mg).

1. temperatureThe mixture was cooled to −70° C.
2. temperatureto warm to room temperature
3. stirringstirred for a further 20 hours
4. temperatureThe mixture was cooled again to −70° C.
5. temperatureto warm to room temperature
6. stirringstirred for a further 32 hours
7. temperaturecooled in ice
8. customquenched with methanol (3 mL)
9. customAfter a further 15 min the mixture was partitioned between dichloromethane (35 mL) and aqueous sodium bicarbonate (35 mL)
10. washThe organic phase was washed again with aqueous sodium bicarbonate (35 mL)
11. customevaporated under reduced pressure
12. customto yield crude material
13. customThis crude product was purified by mass-directed autopreparation